Study on Synthesis of (s)-3-(t-butyldimethylsilyloxy)-7,7-dichloro-2,2-dimethyloctanoic acid

摘要

(s)-3-(t-butyldimethylsilyloxy)-7,7-dichloro-2,2-dimethyloctanoic acid (9), a segment of the new cyclodepsipeptide lyngbyabellin A (14), which exhibits moderate cytotoxycity against human cancer cell lines, was synthesized through six steps. The key stereoselective synthesis of (9) was achieved by the enantioselective aldol reaction developed by Kiyooka. Lyngbyabellin A (14) is a new cytotoxic pepolides isolated from the marine cyanobacterium L. majuscula collected at Finger's Reef, Apra Harbor, Guam. It exhibited moderate cytotoxic properties against human cancer cell lines, KB cells (a human nasopharyngeal carcinoma cell line) and LoVo cells (a human colon adenocarcinoma cell line), with IC_(50) values of 0.03μg/mL and 0.50μg/mL, respectively. In addition, because of its encouraging biological activities and highly unusual bis-thiazole containing structure, we viewed it as a significant and challenging synthetic target.